Boosting immune cells to fight pneumonia without antibiotics
Streptococcal pneumonia is a disease of enormous public health importance, and the emergence of antibiotic-resistant bacterial strains of the illness is making treatment with antibiotics increasingly difficult. Understanding the mechanisms the immune system uses to regulate immune cells called macrophages, which engulf and clear bacteria from the lungs, could lead to alternative treatment strategies that boost the patient’s own anti-bacterial responses to the infection.
IRP researchers led by Darryl Zeldin, M.D., discovered that after macrophages sense foreign bacteria, they cause an enzyme called soluble epoxide hydrolase (sEH) to suppress anti-inflammatory molecules in the body called epoxyeicosatrienoic acids (EETs). Using drugs and genetic manipulation to prevent suppression of the EETs caused bacterial infections to worsen. Conversely, treatment with a compound that increased suppression of EETs accelerated bacterial clearance from the lungs.
The discovery that activating sEH is critical for bacterial clearance may help to explain why certain populations, such as the elderly, are more susceptible to prolonged lung infections. In addition, these studies suggest cautious use of pharmaceutical sEH inhibitors, which are progressing through clinical trials evaluating them as treatments for pain and cardiovascular conditions. Finally, the findings offer the possibility that EET suppressors may provide a non-antibiotic treatment for pneumonia.
Li H, Bradbury JA, Edin ML, Graves JP, Gruzdev A, Cheng J, Hoopes SL, DeGraff LM, Fessler MB, Garantziotis S, Schurman SH, Zeldin DC. (2021). sEH promotes macrophage phagocytosis and lung clearance of Streptococcus pneumoniae. J Clin Invest. Nov 15;131(22):e129679. doi: 10.1172/JCI129679.
This page was last updated on Thursday, June 8, 2023